What’s ahead for rheumatoid arthritis treatment? Scientists say they’ll be more targeted and precise, as well as better at fighting RA symptoms and less likely to cause dangerous side effects. Lifescript looks at the latest advances for this difficult-to-treat inflammatory condition to see what’s coming down the medication pipeline…

In the past 15 years, a revolution has occurred in rheumatoid arthritis treatment.

“Prior to that, we had drugs that helped patients feel and function better, but we weren’t capable of inducing remission,” says rheumatologist Nathan Wei, M.D., director of the Arthritis Treatment Center in Frederick, Md., which is heavily involved in research.

“Now, with the advent of biologic therapies” – drugs like adalimumab (Humira), which are made up of proteins, not chemicals –“remission is what we shoot for,” he says. “With each new generation of biologics, we’re approaching a time when we can think about a cure.”

Biologics are the best RA treatment because they’re more precise than earlier drugs, says Dr. Wei.

“It’s the difference between using a shotgun versus a laser-beamed rifle,” he says. “Before, rheumatoid arthritis drugs suppressed the immune system with no clearly defined target.”

Now, physicians can aim directly at the causes of RA’s chronic inflammation and destruction, he says.

“RA is really a spectrum of diseases, so until we can identify what type a patient has and hit it with the right medicine, we’re still not there.”

Cutting-edge research is attempting to do just that. Read on for some of the most exciting developments, which could lead to new drugs and change the future of rheumatoid arthritis treatment.

1. A new class of biologic drugs reduces inflammation.What they are: JAK inhibitors are oral biologic drugs that inhibit the protein enzyme Janus kinase, which is involved in inflammation.

Why the excitement? For chronic RA inflammation to persist, signals must move from the surface of a protein cell responsible for the inflammation to its nucleus, says Dr. Wei, who’s working on JAK research trials. When the signal reaches the nucleus, the cell begins its dance of inflammation and destruction.

“JAK blocks the signal, so the cell nucleus never gets the message” for inflammation to begin, Dr. Wei says.

Another boon for patients: Unlike other biologic drugs, which are injected, JAK inhibitors are taken orally – making them much more convenient and easier to administer.

Potential pitfalls:Side effects of this rheumatoid arthritis treatment include lowered white blood cell counts (which reduce immunity), kidney abnormalities and elevated blood pressure and cholesterol. (Statin drugs may lower cholesterol, according to a 2011 study at the University of Glasgow in Scotland.)

In fact, four out of 792 participants have died during clinical trials of one JAK inhibitor, tofacitinib.

“Anytime you interfere with the immune system, death is a possibility,” Dr. Wei says. Pfizer, the manufacturer, says that only one death – from respiratory failure – was related to the drug.

Availability:Tofacitinib, approved in 2012, shows significant reduction of signs and symptoms of RA, less joint damage, and more remission at six months compared to a placebo.

2. A tiny molecule could prevent RA symptoms while protecting immunity.What it is: Like JAK inhibitors, Compound 20 is a small molecule that inhibits an enzyme involved in inflammation, but in a slightly different way.

“But instead of just suppressing those, we found that compound 20 also makes peace-making regulatory cells more effective,” says Michael Dustin, Ph.D., a professor of pathology at New York University School of Medicine and one of the authors of a 2010 Compound 20 study.

Unlike other biologics, Compound 20 may not inhibit the immune system’s response to many harmful bacteria or viruses – a real virtue, says Dustin.

Potential pitfalls: Not many, says Dustin.

“They’re not good at fighting parasitic worms,” he says – a specific immune issue that isn’t much of a concern for Americans.

Availability: “It will probably be years – but not decades – until Compound 20 or a similar drug is available,” Dustin says.

3. Another new protein does less damage to the immune system.What it is: ATSTTRIN is a new protein molecule constructed from the growth factor protein progranulin, which the body produces naturally. (The name stands for “antagonist of TNF/TNR signaling via targeting to TNF receptors.”)

It works by inhibiting other molecules that cause inflammation.

Why the excitement: After several weeks of regular injections, mice with mild arthritis appeared free of RA symptoms.

Current remedies that inhibit tumor necrosis factor (TNF) – inflammatory proteins – suppress TNF receptors 1 and 2. That means they restrain a lot of the immune system, leaving patients open to infections.

“But this ATSTTRIN molecule inhibits only TNF receptor 2, yet still is very effective at treating the disease,” Dustin says. “So, if you have a choice between two drugs that are equally effective, it’s better to pick the one that inhibits less of the immune system.”

Potential pitfalls: It needs to be injected, and your immune system could reject it.

“But if your body doesn’t make antibodies to it, it could be a drug candidate,” Dustin says.

Availability: The research is at a much earlier stage than Compound 20. “It could take a decade to develop,” Dustin says.

4. An injectable gel releases medication only where it’s needed.What it is: The gel is ascorbyl palmitate, a modified form of vitamin C recognized as safe by the FDA. (Researchers have also developed several similar gels.)

Why the excitement? Many rheumatoid arthritis drugs are systemic – they’re pills that circulate medication throughout the body, not just to the needed joints. That means doses must be high to be effective.

Trouble is, high doses can be toxic, says Jeffrey Karp, Ph.D., lead gel investigator and co-director of the Center for Regenerative Therapeutics at Brigham and Women’s Hospital in Boston.

An alternative is injections, but the body is very efficient at clearing out injected medicines within minutes or hours.

But the gel is designed to release medication only if inflammatory enzymes are present.

“It’s like a wrapped present,” Karp says. “The gel is a box with medications inside, and inflammatory enzymes cut the ribbons to open the box.”

Potential pitfalls: “None that we know of yet,” although research is still in early stages, says Karp. “There may be certain drugs that are challenging to [put] into gel form.”

Availability: “The gel might enter clinical trials within the next 2-3 years, and they typically take anywhere from 6-10 years,” Karp says. “So it could be a decade or more before it’s on the market.”

5. A molecule mimic seeks and destroys RA disease cells.What it is: In 2009, researchers at Northwestern University in Chicago discovered that a compound called Bim is essentially a “death” protein that removes cells that don’t belong – such as overactive immune cells involved in inflammation and rheumatoid arthritis. People with RA have low Bim levels, the scientists found.

“So we asked ourselves: How can we restore that protein to people with RA?” says Harris Perlman, Ph.D., lead researcher and an associate professor of medicine at Northwestern’s Feinberg School of Medicine.

They solved the problem by making a small molecule, BH3 – “nicknamed the suicide molecule,” Perlman says – that mimics Bim.

Why the excitement: When the BH3 molecule was injected into mice with RA, the damaging immune cells died, decreasing joint swelling and bone destruction.

“When we inject the imitation molecule, it returns the body to normalcy,” Perlman says. “We can give the molecule to healthy mice and then try to give them RA, and they don’t get it. Or we can give the mice RA, and the molecule completely suppresses the RA symptoms.”

Potential pitfalls: “The biggest pitfall for all rheumatoid arthritis drugs is an increase in infection,” because the immune system is suppressed, says Perlman. “But when we injected mice with the molecule daily for three months, none developed infection.”

Availability: Preclinical testing, which includes major studies showing mice aren’t harmed by this rheumatoid arthritis treatment, depends on securing more government and private funds, says Perlman.

“Then we do phase 1 trials with patients,” Perlman says. “I expect it will take five or more years just to get there.”

What’s Your Inflammation IQ?Inflammation has become a hot topic over the last few years. The latest scientific research indicates that inflammation is behind more than 80% of the conditions we suffer from – everything from arthritis to heart disease. Dr. Mark Hyman, author of The UltraSimple Diet, agrees that inflammation leads to a host of health problems. Fighting it can get you on track to a healthier, happier life. Take this inflammation quiz and find out how much you may already know.

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